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Review
. 2021 Oct 22;13(21):5318.
doi: 10.3390/cancers13215318.

"V体育ios版" Targeting Tumor-Associated Macrophages in Cancer Immunotherapy

Amy J Petty  1 , Dwight H Owen  2 , Yiping Yang  3 , Xiaopei Huang  3
Affiliations
Review

Targeting Tumor-Associated Macrophages in Cancer Immunotherapy

Amy J Petty et al. Cancers (Basel). .

Abstract

Tumor-associated macrophages (TAMs) represent the most abundant leukocyte population in most solid tumors and are greatly influenced by the tumor microenvironment VSports手机版. More importantly, these macrophages can promote tumor growth and metastasis through interactions with other cell populations within the tumor milieu and have been associated with poor outcomes in multiple tumors. In this review, we examine how the tumor microenvironment facilitates the polarization of TAMs. Additionally, we evaluate the mechanisms by which TAMs promote tumor angiogenesis, induce tumor invasion and metastasis, enhance chemotherapeutic resistance, and foster immune evasion. Lastly, we focus on therapeutic strategies that target TAMs in the treatments of cancer, including reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to increase TAM-mediated phagocytosis. .

Keywords: cancer; checkpoint inhibitor; immunotherapy; tumor microenvironment; tumor-associated macrophages (TAM). V体育安卓版.

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"VSports手机版" Conflict of interest statement

The authors declare no conflict of interest. DHO reports research funding to institution outside the scope of this work from Genentech, BMS, Merck, Palobiofarma, Pfizer. V体育ios版.

Figures

Figure 1
Figure 1
Functional roles of TAMs. TAMs can promote tumor progression through four main mechanisms: (1) augmenting tumor proliferation; (2) enhancing angiogenesis; (3) promoting metastasis; and (4) suppressing adaptive immune responses. Abbreviations: EGF—epithelial growth factor; PDGF—platelet-derived growth factor; TGF-β—transforming growth factor beta; HGF—hepatocyte growth factor; bFGF—basic fibroblast growth factor, MGF-E8—milk fat globule-EGF factor 8; EC—endothelial cell; VEGF—vascular endothelial growth factor; CCL2—C motif chemokine ligand 2; CXCL8—C-X-C motif chemokine ligand 8; MMPs—matrix metalloproteases; MIP1-β—macrophage inflammatory protein 1 beta; CCL18—C motif chemokine ligand 18; S100A8/9—S100 calcium binding protein A8/9; SPARC—secreted protein acidic and cysteine rich; Arg1—arginase 1; iNOS—inducible nitric oxide synthase; IL-10—interleukin 10; PGE2—prostaglandin E2; CCL17/22—C motif chemokine ligand 17/22; PD-L1/2—programmed death ligand ½; Tex—exhausted T cell; Treg—regulatory T cell. Created with BioRender.com.
Figure 2
Figure 2
TAM-targeting immunotherapies. Current therapeutic strategies have focused on four major aspects—(1) limiting monocyte recruitment to the tumor site; (2) depleting TAMs; (3) reprogramming TAMs; and (4) targeting inhibitory molecules on TAMs. Inhibition is indicated by red circles while activation is marked by green plus signs. Abbreviations: CAF—cancer-associated fibroblast; CCL2—C-C motif chemokine ligand 2; CCR2—C-C motif chemokine receptor 2; CXCL12—C-X-C motif chemokine ligand 12; CXCR4—C-X-C motif chemokine receptor 4; CD11b/CD18—macrophage-1 antigen; CSF1—colony stimulating factor 1; CSF1R—colony stimulating factor 1 receptor; Shh—sonic hedgehog; RIP1—receptor interacting protein 1; PI3K—phosphoinositide 3-kinase; TLR—Toll-like receptor; CD206—mannose receptor; PD-1—programmed cell death protein 1; PD-L1—programmed death ligand 1; CD47—integrin associated protein; SIRPα—signal-regulatory protein alpha; LILRB1—leukocyte immunoglobulin like receptor B1. Created with BioRender.com.
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